What side effects are associated with this type of intervention?

Common side effects of psilocybin, a 5-HT2A receptor agonist used in the treatment of demoralization, include nausea, dizziness, headaches, and transient anxiety or paranoia. More severe psychological effects such as hallucinations and emotional distress can also occur but are typically short-lived.

What prior FDA approvals exist?

Currently, there are no FDA-approved treatments specifically for demoralization. However, psilocybin, a 5-HT2A receptor agonist, is being studied for its potential benefits in altering perception, mood, and cognition, which may help alleviate symptoms of demoralization. Other related drugs that affect serotonin receptors, such as SSRIs, are approved for conditions like depression and anxiety, which share some symptomatic overlap with demoralization.

What other types of research exist?

Promising novel alternatives to Psilocybin for treating demoralization in 2024 may include MDMA-assisted therapy, ketamine or esketamine therapy, and other serotonergic psychedelics like LSD or DMT. Additionally, novel antidepressants such as those targeting the NMDA receptor (e.g., esketamine) or other mechanisms (e.g., rapid-acting antidepressants) could be considered.

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Psychedelic

Psilocybin + Psychotherapy for Demoralization (PATH Trial)

Phase 2

Waitlist Available

Led By Yvan Beaussant, MD

Research Sponsored by Yvan Beaussant

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Psilocybin is very likely to have no genotoxic effects. One study that directly focused on the mutagenic potential of psilocybin did not found this type of toxicity. However, due to the lack of clinical and non-clinical studies on the effects of psilocybin on the developing human fetus, women and men of child-bearing potential and who are sexually active must agree to use an acceptable contraceptive method (hormonal or barrier method of birth control; abstinence) throughout their participation in the study. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of psilocybin administration

Palliative Performance Scale (PPS) ≥ 50 % (see Appendix A)

Must not have

Condition impairing oral intake or digestive absorption

End stage liver disease or cirrhosis as primary hospice diagnosis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through study completion, an average of 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a treatment using psilocybin, a substance from certain mushrooms, combined with talk therapy for hospice patients feeling demoralized. The goal is to see if this approach can safely reduce their emotional distress. Psilocybin recently received breakthrough status by the FDA for its use in treatment of depression.

Who is the study for?

This trial is for adults over 21 in hospice care with any terminal illness, experiencing moderate-to-severe demoralization. They must have a caregiver present after taking the study drug and not drive for 24 hours post-administration. Participants need to use contraception if of childbearing potential. Exclusions include those with certain psychiatric conditions or family history, significant suicide risk, allergies to similar drugs, or on medications that could interact poorly.

What is being tested?

The study tests psilocybin-assisted psychotherapy's effectiveness in reducing feelings of hopelessness among terminally ill patients receiving hospice care. Psilocybin is administered under controlled conditions alongside sessions of psychotherapy to evaluate its impact on demoralization.

What are the potential side effects?

While specific side effects are not listed here, psilocybin can potentially cause changes in sensory perception and mood, confusion, headache, nausea, psychological distress or exacerbation of pre-existing mental health issues during the period it affects the brain.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I agree to use birth control during and 4 months after the study.

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I am mostly independent but may need some help with daily activities.

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I am 21 years old or older.

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I do not have any terminal illness.

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I am 21 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have trouble eating or absorbing food.

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My primary reason for hospice care is end-stage liver disease or cirrhosis.

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My liver tests are very high, or I have signs of liver failure like confusion or yellowing skin.

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I am not taking medications that could badly interact with the study drugs.

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I have a parent, sibling, or child with schizophrenia or bipolar disorder.

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I am currently undergoing chemotherapy.

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I am not pregnant, nursing, or planning to become pregnant.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through study completion, an average of 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through study completion, an average of 1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and through study completion, an average of 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Average time delay from screening to enrollment

Duration of assessment visits

Mean number of sessions completed by enrolled participants

+4 more

Secondary study objectives

Change in Caregiver- CarGOQoL Score

Change in Challenging Experience Questionnaire (CEQ) Score

Change in Global Quality Life Score as assessed by Functional Assessment of Chronic Illness Therapy - Palliative Care 14 (FACIT-Pal 14)

+11 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: PATHExperimental Treatment2 Interventions

The research study procedures include screening for eligibility, and study intervention including preparation, evaluations, one psilocybin session and follow up visits. -The treatment regimen consists of a single administration of psilocybin 25 mg orally combined with a supportive psychotherapy including 2 preparation sessions and 2 integration sessions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Psilocybin

2021

Completed Phase 2

~530

Psychotherapy

2014

Completed Phase 3

~3440

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Psilocybin, a 5-HT2A receptor agonist, works by altering perception, mood, and cognition, which can help patients reframe their experiences and reduce feelings of demoralization. This is particularly important for demoralization patients as it can provide a sense of meaning and reduce existential distress. Other treatments with similar effects include selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), which increase serotonin levels in the brain, thereby improving mood and cognitive function. These treatments are crucial for demoralization patients because they address the underlying neurochemical imbalances that contribute to their symptoms, offering relief from persistent negative thoughts and emotional distress.